MODERATE AND ADVANCED ALZHEIMERS PATIENTS EXHIBIT PLATELET ACTIVATIONDIFFERENCES

We previously reported that platelets from advanced sporadic Alzheimer 's disease (AD) patients exhibit two defects: first, an aberrant signa l transduction presenting as a thrombin-induced hyperacidification, wh ich is more severe for donors with the apolipoprotein E4 allele (apoE4 ), and second, an AD-specific Amyloid Precursor Protein (APP) processi ng defect that presents as retention of APP on the activated platelets ' surface and is independent of the apo E allele. This retention of me mbrane APP correlates with decreased release of soluble APP. To determ ine at what stage in the disease progression these defects appear, we performed signal transduction and secretion studies on moderate AD pat ients. Thrombin-activated platelets from these patients do not exhibit either hyperacidification or APP retention; their APP processing and secretion are normal by Western blotting, suggesting that the two plat elet defects appear in the advanced stages of AD. (C) 1997 Elsevier Sc ience Inc.